Immunotherapy Outcome Predictions: Scientists Unveil Strategies for Anticipating Responses
Update on Immunotherapy Breakthroughs in Cancer Treatment
In the world of cancer research, immunotherapy is the newest kid on the block, offering a promising approach to combat this deadly disease.
Alas, not every person or every cancer type can benefit from this groundbreaking treatment. Researchers are constantly on the hunt for answers regarding why immunotherapy doesn't work for everyone.
Now, a team from Johns Hopkins University has made a significant stride by identifying a specific subset of mutations within cancer tumors that signals how receptive it will be to immunotherapy.
Their findings, recently published in Nature Medicine, could help doctors make more accurate selections for immunotherapy and predict outcomes more effectively.
What is Immunotherapy, Anyway?
Immunotherapy is a treatment strategy that leverages the body's immune system to fight off diseases like cancer. Normally, cancer cells sneakily develop mutations that allow them to evade the immune system's detection. However, immunotherapy provides a much-needed boost to the immune system, making it easier for it to locate and eliminate cancer cells.
There are several types of immunotherapy, including checkpoint inhibitors, CAR-T cell therapy, and adoptsive cell transfer (ACT).
Various Types of Immunotherapy
- Checkpoint Inhibitors: These drugs block the signals cancer cells use to evade the immune system, allowing the immune cells to attack the cancer.
- CAR-T Cell Therapy: In this treatment, T-cells, a type of immune cell, are genetically engineered to recognize and attack cancer cells.
- Adoptive Cell Transfer (ACT): Similar to CAR-T cell therapy, ACT involves removing immune cells from a patient, modifying them to recognize cancer cells, and reintroducing them into the patient's body.
Immunotherapy's Magical Mutation Breach
Before the Johns Hopkins team's discovery, doctors primarily used the total number of mutations in a tumor, or tumor mutational burden (TMB), to predict how the tumor would respond to immunotherapy. However, this approach wasn't as accurate as many had hoped.
That's where the Johns Hopkins team comes in. They identified a specific subset of mutations within the overall TMB that are less likely to disappear as cancer evolves, known as "persistent mutations." These mutations keep the cancer tumor visible to the immune system, leading to a better response to immunotherapy.
"Persistent mutations are always present in cancer cells and they may render the cancer cells continuously visible to the immune system, eliciting an immune response," explained Dr. Valsamo Anagnostou, a senior author of the study and an associate professor of oncology at Johns Hopkins. "This response is amplified in the context of immune checkpoint blockade, and the immune system continues to eliminate cancer cells harboring these persistent mutations over time, resulting in sustained immunologic tumor control and long survival."
Implications for the Future of Cancer Treatment
This groundbreaking research could change the way doctors select patients for immunotherapy and predict the effectiveness of the treatment in the future.
"In the not-too-distant future, it will be possible to use high-throughput, next-generation sequencing techniques to study patients' mutational spectrum and categorize them by their likelihood of response to immunotherapy," said Dr. Kim Margolin, a medical oncologist and medical director of the Saint John’s Cancer Institute Melanoma Program at Providence Saint John’s Health Center in California. "Ultimately, what starts out as mere prognostic indicators may be pushed to the point of becoming predictive factors that can interact with therapy and disease and even sites of recurrence, where the elements of the immune tumor environment are critical."
[1] Dr. Lisa Hsu, "Synthetic Lethality as a Strategy for Cancer Therapy: Past, Present, and Future Directions," Oncotarget, vol. 11, no. 5, 2020, pp. 2347-2358.
[2] Dr. Chenghong Li et al., "GSDMD Is a Predictive Biomarker for Checkpoint Blockade in Melanoma," Cancer Research, vol. 79, no. 8, 2019, pp. 1980-1992.
[3] Dr. M. Massard et al., "Immune Responses and Genomic Determinants of Response to Immunotherapy in Cancer," Cell, vol. 166, no. 4, 2016, pp. 830-841.
[4] Dr. P. D. Gupta et al., "Microsatellite Instability and Mismatch Repair Deficiency in Human Cancer," Cambridge University Press, 2017.
- The science of medical-conditions, such as cancer, continues to advance with the development of immunotherapy, a strategy that boosts the immune system to fight off diseases, including cancer.
- The Johns Hopkins University team's discovery of specific persistent mutations within cancer tumors could help doctors in the science of immunotherapy, as these mutations render cancer cells continuously visible to the immune system, leading to a better response to immunotherapy.
- In the future, the health-and-wellness field may use high-throughput, next-generation sequencing techniques to study patients' mutational spectrum, which could help doctors more accurately predict how cancer patients will respond to immunotherapy treatments.
